Biocompatible hydrogels for cartilage repair or as interpositional devices require mechanical integrity, high water content, and excellent lubricity to fully function under the high stress environment in the human joint spaces. Hydrogels are good candidates for such purposes, but currently available hydrogels do not provide sufficient mechanical strength, creep resistance, and lubricity compatible to that of natural articular cartilage. Most hydrogels systems available for articular cartilage repair or replacement applications do not have required mechanical strength to withstand the high loads of the human joint. Various dehydration methods, described below, can be used together in combinations to alter the properties of hydrogels.
Solvent dehydration of hydrogels is described by Bao (U.S. Pat. No. 5,705,780). Bao describes immersion of PVA hydrogel into solvents such as ethanol/water mixture at room temperature to dehydrate PVA hydrogel without shape distortion.
Hyon and Ikada (U.S. Pat. No. 4,663,358) and Bao (U.S. Pat. No. 5,705,780) describe the use of water and organic solvent mixture to dissolve PVA powder and subsequently cooling the solution below room temperature and heating back up to room temperature to form a hydrogel. The hydrogel is then immersed in water to remove the organic solvent. Hyon and Ikada contend that PVA hydrogels thus formed are transparent, as opposed to the ones formed by freeze-thaw method that uses water only as the solvent to dissolve the PVA powder. Freeze-thaw gels are described in the U.S. Pat. No. 5,705,780.
Bao (U.S. Pat. No. 5,522,898) describes dehydration methods that use air dehydration, vacuum dehydration, or partial humidity dehydration to control the rate of dehydration and prevent shape distortion of PVA hydrogels for use as prosthetic spinal devices to replace the nucleus pulpous.
Ku et al. (U.S. Pat. No. 5,981,826) describes a freeze-thaw method to form a PVA hydrogel by subjecting a PVA aqueous solution to freeze-thaw followed by immersion in water and additional cycles of freeze-thaw while immersed in water.
The creep resistance of PVA is currently achieved in the field by reducing the equilibrium water content (EWC) of the hydrogel, which also reduces the lubricity of the hydrogel. The strength and the creep resistance of a hydrogel can be increased by methods described elsewhere (see Muratoglu et al., WO 2006/132661). The lubricity of the hydrogel can be increased by increasing the hydrophilicity of the hydrogel (see Muratoglu et al., U.S. provisional patent application Nos. 60/913,415, filed Apr. 23, 2007; and 60/913,618, filed Apr. 24, 2007).
Same hydrogels lack the presence of ionic components/moieties. Cartilage is a composite structure containing ionic moieties, which are along the backbone of the glucoseaminoglycan (GAG) molecules. The GAGs are polymers of disaccharides that contain alternating sequences of glucuronic acid (GlcA) and either N-acetylglucosamine (GlcNAc) or N-acetylgalactosamine (GalNAc). The GAG family members, including hyaluronic acid (HA), chondroitin sulfate (CS), keratan sulfate (KS), and heparan sulfate (HS), plays an important role in the mechanical and transport properties of extracellular matrix (for example, CS, HA) (see Grodzinsky et al., Annu. Rev. Biomed. Eng. 2000, 2:691-713) and in cell surface ligand binding interactions (for example, HS) (see Lander et al., J. Cell. Biol. 2000, 148:227-232). For example, chondroitin sulfate GAG (CS-GAG) contains on the average one negatively charged carboxylate and sulfate group per disaccharide which is ionized under physiological pH conditions. Therefore, the high negative charge density and associated electrical repulsion between CS-GAGS play an important role in electromechanical and physicochemical interaction within biological tissues such as cartilage. The role of electrical repulsive interactions can be important in articular cartilage, providing compressive and shear stiffness during the relative motion of opposing joint surfaces. The compressive resistance of cartilage is mainly due to highly charged CS-GAGs, which are attached to a core protein, forming the proteoglycan known as aggrecan (see Moonsoo and Grodzinsky, Macromolecules 2001, 34:8330-8339). These ionic moieties also increase the ability of the cartilage to hold water. In an effort to design a synthetic hydrogel to mimic the properties of cartilage it is also important to have ionic moieties to mimic the role of the GAG molecules. Therefore, there remains a long felt but unmet need for a creep resistant, highly lubricious, and tough cartilage-like ionic hydrogel composition having ionic moieties and increased the ability to hold water and mechanical strength. Such a creep resistant, highly lubricious, tough and ionic hydrogels comprising polyacrylamido-methylpropane sulfonic acid (PAAMPS) and methods of making such a composition were not known until the instant invention. Others have failed in such endeavors.